Orthotopic liver transplantation (OLT) is now a well- established means of restoring health in patients with end stage liver disease. Our long-term objective is to provide evidence- based information to help optimize the outcome of OLT, which is relevant not only at the individual physician and patient level, but also at the health policy level. Building on our achievements from the previous program period and data collaboration from a network of academic transplant centers, we propose to study the three most important issues that face liver transplantation in the United States today. In specific aim 1, we will prospectively validate the Model for End-stage Liver Disease (MELD) in current OLT candidates. The MELD scale, a liver disease severity index developed by this program, has recently been adopted by the United Network for Organ Sharing (UNOS) as the national liver allocation system for OLT. Our central hypothesis is that the addition of further variables to the model will not materially improve the model, except in patients with hepatocellular carcinoma, in whom the risk of tumor progression needs to be considered in addition to the severity of underlying liver disease. In specific aim 2, we will identify determinants of the outcome of recurrent hepatitis C following OLT. OLT recipients with hepatitis C, the most common indication for the procedure today, have shorter survival and poorer quality of life. Our hypothesis is that pretransplant alcohol consumption and post-transplant obesity affect the rate of progression of recurrent hepatitis C and thus, the outcome. In specific aim 3, we will study the cardiovascular morbidity in long-term survivors following OLT. Based on the number of patients and length of follow-up available in our database, we will identify traditional (e.g., diabetes, hypertension, and hyperlipidemia) and transplant-specific (e.g., cytomegalovirus infection and liver disease diagnosis) risk factors that are associated with cardiovascular complications. The results of these studies will provide relevant information not only to clinicians in practice, but also transplantation policy makers. The feasibility of the proposed projects is supported by the extensive experience and track record of this program in creating and maintaining a large, multicenter, liver transplant database and strong statistical expertise.